期刊
HUMAN MOLECULAR GENETICS
卷 26, 期 13, 页码 2577-2588出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddx151
关键词
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资金
- German Research Foundation DFG (Deutsche Forschungsgemeinschaft) [GZ: SCHA 1582/3-1]
- German Ministry of Education and Research through POPGEN [01GR0468]
- German Migraine & Headache Society (DMKG)
- Almirall
- Astra Zeneca
- Berlin Chemie
- Boehringer
- Boots Health Care
- Glaxo-Smith-Kline
- Janssen Cilag
- McNeil Pharma
- MSD Sharp Dohme
- Pfizer
- Institute of Epidemiology and Social Medicine University of Muenster
- German Ministry of Research and Education (BMBF) [01ER0816]
- Federal Ministry of Education and Research BMBF [FKZ 0315540A]
- Heinz Nixdorf Foundation (Germany)
- German Ministry of Education and Science
- German Research Council (DFG) [SI 236/8-1, SI236/9-1, ER 155/6-1]
- German Centre for Neurodegenerative Diseases (DZNE), Bonn
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03IS2061A, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- GABA, Switzerland
- Siemens Healthcare, Erlangen, Germany
- Federal State of Mecklenburg, West Pomerania
- [BMBF-01-ZZ-9603/0]
Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. The disease is characterized by destruction of the alveolar bone due to an aberrant host inflammatory response to a dysbiotic oral microbiome. Previous genome-wide association studies (GWAS) have reported several suggestive susceptibility loci. Here, we conducted a GWAS using a German and Dutch case-control sample of aggressive periodontitis (AgP, 896 cases, 7,104 controls), a rare but highly severe and early-onset form of periodontitis, validated the associations in a German sample of severe forms of the more moderate phenotype chronic periodontitis (CP) (993 cases, 1,419 controls). Positive findings were replicated in a Turkish sample of AgP (223 cases, 564 controls). A locus at SIGLEC5 (sialic acid binding Ig-like lectin 5) and a chromosomal region downstream of the DEFA1A3 locus (defensin alpha 1-3) showed association with both disease phenotypes and were associated with periodontitis at a genome-wide significance level in the pooled samples, with P = 1.09E-08 (rs4284742,-G; OR = 1.34, 95% CI = 1.21-1.48) and P = 5.48E-10 (rs2738058,-T; OR = 1.28, 95% CI = 1.18-1.38), respectively. SIGLEC5 is expressed in various myeloid immune cells and classified as an inhibitory receptor with the potential tomediate tyrosine phosphatases SHP-1/-2 dependent signaling. Alpha defensins are antimicrobial peptides with expression in neutrophils andmucosal surfaces and a role in phagocyte-mediated host defense. This study identifies the first shared genetic risk loci of AgP and CP with genome-wide significance and highlights the role of innate and adaptive immunity in the etiology of periodontitis.
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